Nadal breezed to a 6-2, 6-1, 6-0 nighttime victory that took only 90 minutes to complete.
Having reached the championship match in six of his last eight Grand Slam appearances, Nadal will next meet Ivan Dodig.
Dodig also had an easy time in the second round while eliminating Nikolay Davydenko 6-1, 6-4, 6-4.
Ferrer, seeded fourth, advanced by outlasting Roberto Bautista Agut 6-3, 6-7 (5-7), 6-1, 6-2. The seventh-seeded Federer coasted to a 6-3, 6-2, 6-1 decision over Carlos Berlocq and Isner, playing late at night, survived against Gael Monfils 7-5, 6-2, 4-6, 7-6 (7-4).
Ferrer will meet Mikhail Kukushkin in the third round, Federer will take on Adrian Mannarino and Isner will play Philipp Kohlschreiber.
Also reaching the third round was Jack Sock, who defeated Maximo Gonzalez 7-6 (7-3), 1-6, 7-5, 6-2.
Notable deaths of 2014 [PHOTOS]